Rapid Genetic Testing Reveals Hidden Cases of Rare Immune Disorders

Researchers at Columbia University Vagelos College of Physicians and Surgeons have developed a groundbreaking laboratory method that significantly enhances the diagnosis of genetic immune system disorders. This innovative approach enables clinicians to rapidly identify patients with suspected genetic conditions, many of whom have been in diagnostic uncertainty for years. Applying this technique to activated-PI3Kδ syndrome (APDS), a rare inherited immune disorder, the team uncovered numerous previously unrecognized genetic variations that could cause the disease.

Published in the journal Cell on June 20, 2025, the study employed a CRISPR-based base editing technology to generate thousands of mutations within known APDS genes. By analyzing the effects of these mutations on healthy human T cells, the researchers could classify genetic variants as either contributing to or harmless concerning the disease. This proactive classification approach expedites diagnosis, allowing for timely and targeted treatment.

One notable application of this method has been the diagnosis of a patient with APDS, who is now receiving the FDA-approved drug leniolisib, which targets the faulty protein associated with the syndrome. Such rapid diagnosis is crucial because effective treatment options are available for APDS, and early intervention can considerably improve patient outcomes. The researchers believe their method may help identify more individuals affected by APDS than previously thought. In fact, genome analysis from over 630,000 Americans suggests that the prevalence could be as high as one in 10,000, far exceeding earlier estimates.

Beyond APDS, this technique holds promise for a broad range of genetic diseases. By systematically evaluating variants of uncertain significance (VUS), clinicians can better interpret genetic tests, moving beyond simply detecting the presence of a variant to understanding its functional impact. This could revolutionize the field of genomics, contributing to a new era where genetic data directly informs personalized medicine.

The team’s findings also suggest that some rare diseases may be more common than previously believed. The identification of potential disease-causing variants in a sizable portion of the population emphasizes the importance of awareness among healthcare providers and the value of comprehensive genetic screening. As researchers continue to adapt this method to other immune disorders and genetic conditions, they hope to enhance diagnostic accuracy, facilitate early treatment, and ultimately improve patient care.

Source: https://medicalxpress.com/news/2025-06-hidden-cases-rare-disease-uncovered.html